Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. G
eneration of NO, a proinflammatory substance on bronchial epithelial cells,
is increased by ACEI Using a randomized, double-blind, placebo-controlled
trial, we tested the hypothesis that supplementing iron, an inhibitor of NO
synthase, may reduce the cough associated with ACEI use. The subjects were
19 patients who had developed ACEI-induced cough. After a 2-week observati
on period, they were randomized to a daily morning dose of either 256-mg fe
rrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The
subjects were requested to rill out a cough diary by scoring the daily sev
erity of the cough on a scale of 0 to 4. Mean daily cough scores for the la
st week of the observation and treatment period were compared. Changes in b
lood cell count and serum iron and ferritin concentration between the 2 per
iods were evaluated. Mean daily cough scores during the observation and tre
atment periods were 3.07 +/-0.70 and 1.69 +/-1.10, respectively, for the ir
on group and 2.57 +/-0.80 and 2.35 +/-1.22, respectively, for the placebo g
roup, showing a significant reduction in cough scores with iron supplementa
tion (P<0.01) but not with placebo. Three subjects in the iron group showed
almost complete cough abolition. No significant changes in laboratory data
were observed in either group. In conclusion, iron supplementation success
fully decreases ACEI-induced cough. This effect may be related to the decre
ase of NO generation associated with the inhibition of NO synthase activity
in bronchial epithelial cells.